It is proposed to continue our investigation of how inorganic fluorine compounds alter the production of cAMP and glucose metabolism in intact cells. During the last four years we have shown that acute and chronic administration of NaF would increase tissue cAMP levels and alter glucose metabolism in the liver. It is planned to extend these observations to determine which enzyme activities (e.g., enolase, pyruvate kinase, phosphorylase etc.) are altered in both chronic and acutely administered NaF to rats. These studies will provide information as to the metabolic effects of inorganic fluorine compounds. One of the factors that govern the diffusion of fluoride (asHF) across biological membranes is the transmembrane pH gradient. Experiments are planned to examine the effects of low concentrations of NaF on cAMP and glucose production under conditions where the pH of the extracellular medium is changed from a "normal" pH of 7.4 to a low pH of about 7.0 and a high pH of about 8.0. These experiments will provide information on how acid-base changes in the extracellular medium effect the response to NaF.